Meeting Theme: Transcription and Chromatin

BY KAROLIN LUGER AND QIANG ZHOU

The "Transcription/Chromatin" annual meeting theme will contain sessions titled: "Structural Transitions in Chromatin - An Exploration of Mechanisms," "Alternative Chromatin Structures," "RNA Polymerase Pausing and Elongation" and "Transcriptional Regulation in Growth, Differentiation and Diseases." The meeting will be held April 9-13, 2011, in Washington, D.C. (Titled "Chromatin and Transcription: A Symbiotic Relationship" in print version.)

Karolin Luger

Qiang Zhou

Transcription and chromatin always have had an intimate, if somewhat unbalanced, relationship. During most of the past three decades, transcription meetings have featured only a somewhat decorative chromatin-related session. Most of the excitement has been in describing TBP, TAFs, transcription initiation apparatus and gene activation mechanisms that impinge on this apparatus. Gradually, the balance tipped when the central role of chromatin was pushed to the foreground through the discovery of transcription activators that serve as histone acetyltransferases. Since then, the roles of numerous posttranslational modifications of histones in transcriptional control have been elucidated. Most recently, things have been as they should be in a good relationship: The two subjects have been on an equal footing, with lots of communication and synergies between them. Their distinction has become blurred, and we have realized that eukaryotic transcription, in all its complexity, functions in the context of chromatin and is regulated by its multilayered structural organization. Likewise, chromatin structure is responsive to complicated manipulations by the cellular machinery that make the DNA more or less accessible for the transcriptional apparatus.

Structural Transitions

In the upcoming thematic session titled “Transcription/Chromatin,” we have chosen topics that echo this symbiotic relationship. A session titled “Structural Transitions in Chromatin - An Exploration of Mechanisms” will highlight cutting-edge technologies devoted to studying the complexity of chromatin structure beyond the nucleosome.

Michelle D. Wang (Investigator, Howard Hughes Medical Institute, Cornell University) will discuss mechanical studies of nucleosome stability and structure and how DNA in nucleosomes may be accessed by motor proteins that are responsible for transcription-related chromatin remodeling. Michael G. Poirier (The Ohio State University) will present studies of post-translational modifications located within the DNA-histone interface, revealing that they function to controllably unlock different forms of nucleosome dynamics. And, James McNally (National Institutes of Health) will discuss progress in measuring transcription factor dynamics at specific promoters, and throughout the genome, using light microscopy in the living cell.

Alternative Structures

A session titled “Alternative Chromatin Structures” will illuminate the fact that nucleosome and chromatin structure is affected by many factors that contribute to the transcription processes.

Steven Henikoff (Investigator, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center) will present intriguing evidence that centromeric nucleosomes wrap DNA in a right-handed orientation, opposite that of left-handed canonical nucleosomes. Karolin Luger (Investigator, Howard Hughes Medical Institute, Colorado State University) will expand on our existing knowledge of nucleosome structures by illuminating the effects of post-translational modifications and of histone variants, as well as of chromatin assembly intermediates. Rui Ming Xu, (Institute of Biophysics, Chinese Academy of Sciences) will report structural and biochemical studies of several histone methyltransferases and methylhistone binding proteins, which have provided an in-depth understanding of histone methylation in regulation of higher order chromatin structure.

RNA Polymerase Pausing

Recent progress in the transcription field has also fundamentally changed our view of the primary regulatory step during gene activation. For a long time, the recruitment of the RNA polymerase (Pol) II transcription initiation apparatus to promoters was considered the major rate-limiting step for the expression of most eukaryotic genes. Recently, a paradigm shift has occurred with the demonstration that the expression of a very large number of metazoan genes, particularly those involved in developmental control, is controlled at the elongation stage. These genes contain paused Pol II at their promoter-proximal regions and are in a state of suspended transcription, which resumes rapidly upon stimulation. The widespread existence of paused Pol II in metazoan genomes suggests that elongation plays a prominent and general role in controlling gene expression.

To reflect this paradigm shift, a session will be devoted to RNA polymerase pausing and elongation. David H. Price (University of Iowa) will present studies on how the positive transcription elongation factor P-TEFb, which causes the transition of paused Pol II into a productively elongating state, is controlled by reversible association with the 7SK snRNP and how gene specific regulation is achieved by coordinating the release of P-TEFb from 7SK snRNP and recruitment to specific targets. David S. Gilmour (The Pennsylvania State University) will examine the basis of promoter proximal pausing via biochemical and in vivo analysis of the association of a negative elongation factor, NELF, with the paused promoters. And, Julia Zeitlinger (Stowers Institute for Medical Research) will explore the mechanism of Pol II pausing in the Drosophila embryo using genome-wide techniques that map protein-DNA interaction, computational methods and genetics.

Transcriptional Regulation

Human diseases often are associated with aberrant gene expression. A session titled “Transcriptional Regulation in Growth, Differentiation and Diseases” will explore how alterations of a cell’s transcriptional program can lead to aberrant phenotypes of multiple diseases. Anders Näär (Massachusetts General Hospital Cancer Center) will present studies on conserved gene regulatory circuits governing cholesterol/lipid homeostasis. The investigation of the SREBP family of transcription factors, which are “master regulators” of both cholesterogenic and lipogenic genes, will offer insights into disease mechanisms and potential therapeutic avenues. Jorge Iñiguez-Lluhí (University of Michigan Medical School) will demonstrate how a reversible modification called SUMOylation regulates the androgen receptor and how alterations in this program contribute to the pathophysiology of three androgen receptor diseases involving sexual differentiation, cancer and neurodegeneration. Finally, to close the loop between human diseases and elongation control, Qiang Zhou (University of California, Berkeley) will present evidence indicating that the HIV Tat protein recruits the host cellular elongation machinery to stimulate viral transcription and that this mechanism could be exploited to disrupt HIV latency for the subsequent elimination of the latent reservoir.

The chromatin/transcription field has never failed to produce novel, cutting-edge discoveries. The recent years have witnessed an acceleration of the pace of our discoveries. The upcoming American Society for Biochemistry and Molecular Biology session on this topic will once again provide an exciting opportunity for us to be in close contact with the major growth points of this ever-growing and fast-evolving field.

Karolin Luger (Karolin.Luger@ColoState.edu) is a Howard Hughes Medical Institute investigator and a university distinguished professor at Colorado State University. Qiang Zhou (qzhou@berkeley.edu) is a professor of biochemistry and molecular biology at the University of California, Berkeley.

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